There are three overarching goals for the proposed renewal: a) further document in detail the biology, epidemiology and behavior of aging among the Tsimane, a forager-horticultural society living in a pre-modern context, and how it changes with acculturation, utilizing further modern methodologies and individual longitudinal data; b) test the hypothesis that aging among the Tsimane is accelerated relative to people in developed nations due to the heavy burden of infectious disease and low energy balance; and c) evaluate a specific theory of human life history and aging developed by the PIs during the course of their research program. To accomplish these goals, there are three specific aims of this competitive renewal. Aim 1 is to obtain longitudinal sampling of physical and cognitive function, energy production, morbidity, co- morbidity, mortality, and social roles after age 40. Aim 2 is to determine rates of immunosenescence for both the acquired and innate arms of the immune system. Aim 3 is to determine rates of vascular, heart and kidney disease, and their associated etiological processes. The continuation of this project will allow us to build a longitudinal profile of a large sample of persons who span the adult age range and to model interactions between infection, nutrition, organ functioning and damage, and physical and cognitive functioning in a population that reached maturity in a pre-modern, highly infectious environment. For each of the four specific aims, we will both compare our results to those obtained in the U.S. and other countries, and model individual variation within the Tsimane population. We will also assess the effects of the within-population variance in acculturation at both the community and individual levels on those outcome variables. In so doing, we will model the effects of changing economic activities, housing conditions, use of medical facilities, Spanish competency, and literacy, and link them to data on health, physical and cognitive status, and mortality. The developing gradients of infection and life expectancy or mortality will provide further data to explore evolutionary hypotheses and to explore the details of the relationships between infection, inflammation and the pathophysiology of aging. PUBLIC HEALTH RELEVANCE: This renewal will provide detailed information on the impacts of infectious disease on health, functional status and mortality in a pre-modern population of forager-horticulturalists of South America experiencing similar demographic conditions as those in mid-19th century Europe. Investigation of arterial, heart and kidney disease in a large sample of older adults can reveal unique insights about the relative contributions of diet, energy expenditure and inflammation due to disease on the rate of physiological aging. In all societies including the contemporary American experience. The results, combined with measures of aging and disease in other populations such as the U.S., Mexico and Indonesia, may help to explain the historical increases in life expectancy over the past several centuries.